Magon A, Leipzig R M, Bloom K, Brewer G J
Prog Clin Biol Res. 1981;55:709-24.
To summarize our results and their implications, by adding induced mouse liver microsomes to an in vitro test for the hemolytic potential of a drug in G6PD deficiency, we found that: 1) Hydroxylation appears to play an important role in activating the hemolytic potential of many drugs. 2) Use of an in vitro test system combining drug, hydroxylation system and red cell, appears to be very reliable in ruling out hemolytic potential, when it is in fact absent, and about 80% effective in identifying hemolytic potential when it is present. 3) Acetylation seems to markedly reduce the hemolytic potential of two drugs studied: promizole and DDS. The genetic polymorphism in acetylation may explain the bimodal response to promizole. 4) These studies suggest that interaction among three pharmacogenetic systems produces a given hemolytic result. Variability of hydroxylation and acetylation rates can be expected to contribute to variability in individual responses to certain hemolytic drugs.
总结我们的研究结果及其意义，通过在体外测试中加入诱导型小鼠肝微粒体，以检测药物在葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症中的溶血潜力，我们发现：1）羟基化似乎在激活许多药物的溶血潜力方面起着重要作用。2）使用结合药物、羟基化系统和红细胞的体外测试系统，在实际上不存在溶血潜力时，似乎能非常可靠地排除溶血潜力；而在存在溶血潜力时，约80%有效地识别溶血潜力。3）乙酰化似乎能显著降低所研究的两种药物——丙咪嗪和氨苯砜的溶血潜力。乙酰化的遗传多态性可能解释了对丙咪嗪的双峰反应。4）这些研究表明，三种药物遗传学系统之间的相互作用产生了特定的溶血结果。羟基化和乙酰化速率的变异性预计会导致个体对某些溶血药物反应的变异性。
